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Antioxidants found to be effective in treating mitochondrial disease, preclinical trials find

In their study, the researchers examined seven antioxidant compounds in two animal models of mitochondrial disease: Zebrafish (Danio rerio) and the worm species Caenorhabditis elegans. In addition, they used cultures of fibroblasts or skin cells obtained from human patients as a third model. All of the models, the patient cells and the experimental animals, had genetically based malfunctions of the mitochondrial respiratory chain (RC). This is an essential part of the mitochondria wherein cells process nutrients and oxygen to produce chemical energy.

One primary factor prevalent in RC disease is oxidative stress, which adds to the worsening of the disease. Antioxidants are generally believed to help neutralize oxidative stress. However, some antioxidants can have adverse side effects, be ineffective, or be used at harmful doses. The antioxidants tested in the study included N-acetylcysteine (NAC), vitamin C, coenzyme Q10 and a type of coenzyme Q10 specifically targeted at mitochondria, vitamin C, lipoate, and orotate.

In the study, researchers found that the two compounds, the drug NAC and vitamin E, significantly affected mitochondrial disease in the animal models. They extended lifespan in mitochondrial complex I disease worms and protected complex I disease zebrafish from brain damage. In addition, NAC enhanced survival in the patient cells. Additionally, these compounds were effective in mitigating oxidative stress that was present not only within the mitochondria but throughout the whole cell.

“Both NAC and vitamin E are the lead antioxidant candidates from this work to be evaluated in clinical trials, to determine whether they effectively benefit the survival, function and feeling of mitochondrial disease patients,” said Marni J. Falk, leader of the study.

Although, coenzyme Q10 and a type of coenzyme Q10 specifically targeted at mitochondria enhanced some indicators of animal health in the worms, they prolonged their lifespan only to a limited extent. Meanwhile, the other three antioxidants tested showed more inconsistent effects than those observed with the other compounds.

“Overall, these pre-clinical model animal data demonstrate that several classical antioxidant drugs do yield significant benefit on viability and survival in primary mitochondrial disease, where their major therapeutic benefit appears to result from targeting global cellular, rather than intramitochondria-specific, oxidative stress,” the researchers wrote.

The findings of the study were published in the journal Molecular Genetics and Metabolism.

More on mitochondrial disease

Mitochondrial diseases occur when the mitochondria of the cells do not work properly. Mitochondria are responsible for producing more than 90 percent of the energy required by the body to sustain life and support organ function. Therefore, when they fail, the energy generated within the cell declines. This is followed by cell injury, and will eventually lead to cell death. Unfortunately, the body organ systems will start to fail if this process is repeated throughout the body. The heart, brain, muscles, and lungs are the most affected organs as they need the greatest amount of energy to function properly.

Diagnosing this disease may be difficult as it affects each person differently. Its symptoms can include seizures, strokes, severe developmental delays, failure to walk, talk, see, and digest food combined with other complications. Moreover, if three or more organ systems are involved, mitochondrial disease should be suspected. (Related: Mitochondrial diseases on the rise – Are GMOs, Roundup to blame?)

Read more news stories and studies on diseases that affect the cells by reading Research.news.